(2R)-Oxiran-2-ylmethyl butanoate → 3-(4-(3-t-Butyldimethylsilyloxy-1-azetidinyl)-3-fluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one

HRID 1418651Notes

Reaction equation

HRID 1418651 reaction equation
[C:1]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:21][CH:20]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH2:19]2)=[C:14]([F:30])[CH:13]=1)([O:3]CC1C=CC=CC=1)=[O:2].[C:31](OC[C@@H]1OC1)(=[O:35])[CH2:32][CH2:33]C>O1CCCC1>[Si:23]([O:22][CH:20]1[CH2:19][N:18]([C:15]2[CH:16]=[CH:17][C:12]([N:11]3[CH2:33][C@H:32]([CH2:31][OH:35])[O:3][C:1]3=[O:2])=[CH:13][C:14]=2[F:30])[CH2:21]1)([C:26]([CH3:27])([CH3:29])[CH3:28])([CH3:25])[CH3:24]

Participants

4

Reactant 2

HCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 70193876N-(carbobenzyloxy)-4-[3-[(tert-butyldimethylsilyl)oxy]-1-azetidinyl]-3-fluoroaniline

Product 1

HCID 213565963-(4-(3-t-Butyldimethylsilyloxy-1-azetidinyl)-3-fluorophenyl)-5(R)-hydroxymethyloxazolidin-2-oneYield 75.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of N-(carbobenzyloxy)-4-[3-[(tert-butyldimethylsilyl)oxy]-1-azetidinyl]-3-fluoroaniline (6.30 g, 14.7 mmol) in dry tetrahydrofuran (100 mL) under a nitrogen atmosphere was cooled to -78° C. and treated with n-butylithium (9.16 mL of a 1.6M solution in hexanes, 14.7 mmol). When the addition was complete, the reaction mixture was stirred at -78° C. for 15 min and then treated with (R)-glycidyl butyrate (2.21 mL, 14.7 mmol). After completion of the addition, the cooling bath was removed and the reaction mixture allowed to stir at ambient temperature for 1.5 h. After this time, saturated aqueous ammonium chloride (20 mL) was added. After 3 min, saturated aqueous sodium bicarbonate (10 mL) was added to the reaction mixture and the organic solvent removed by rotary evaporation under reduced pressure. Dichloromethane (100 mL) was added and the mixture washed with water and brine. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. Chromatography over silica gel (200 g), eluting with a gradient of 1-3% methanol/chloroform, afforded, after concentration of appropriate fractions, 4.39 g (75%) of the title compound as an off-white solid with mp 183°-186° C. and MS(EI) 396 (M+).

Workup

  1. additionWhen the addition
  2. additionAfter completion of the addition
  3. customthe cooling bath was removed
  4. stirringto stir at ambient temperature for 1.5 h
  5. additionAfter this time, saturated aqueous ammonium chloride (20 mL) was added
  6. waitAfter 3 min
  7. additionsaturated aqueous sodium bicarbonate (10 mL) was added to the reaction mixture
  8. customthe organic solvent removed by rotary evaporation under reduced pressure
  9. additionDichloromethane (100 mL) was added
  10. washthe mixture washed with water and brine
  11. dry with materialThe organic layer was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. washChromatography over silica gel (200 g), eluting with a gradient of 1-3% methanol/chloroform
  15. customafforded

Sources & evidence

ORD record
ord-b99ccc2a559d4e328400ef75024630a3
Source dataset
uspto-grants-1999_03
Patent number
US05883093

Reaction notes

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